Immunologic Research

, Volume 65, Issue 1, pp 402–409 | Cite as

Tolerance, loss of tolerance and regaining tolerance to self by immune-mediated events

  • Arpad Zsigmond Barabas
  • Chad Douglas Cole
  • Richard Milton Graeff
  • Rene Lafreniere
  • Donald Mackay Weir
Mechanism in Autoimmunity


Autoimmunity has both beneficial and harmful aspects. Beneficial aspects include: (1) removal of released intracytoplasmic antigens (ags) (cells at the end of their life span or damaged by outside agents) by specific nonpathogenic IgM autoantibodies and mononuclear cells and (2) recognition and elimination of cancerous cells. In contrast, harmful aspects include: (1) mounting a pathogenic autoimmune response against a tissue-derived ag, a ‘modified self,’ resulting in autoimmune disease and (2) inability to recognize and eliminate a cancerous clone. The immune system continuously faces internal and external influences; however, even when it is compromised or overwhelmed, it will still endeavor to regain and maintain tolerance to self. To promote this, we developed a ‘modified vaccination technique’ (MVT) (described as the third vaccination method after active and passive immunizations). It has two components: purified exogenous/endogenous ag (i.e., target ag) and a high-titer-specific antibody (ab) against the target ag made into an immune complex (IC) with predetermined immune-inducing components. The MVT works by ab information transfer (production of same class of immunoglobulin with the same specificity against the target ag that is present in the vaccine), thereby re-establishing tolerance to self (caused by exogenous/endogenous ags) following repeated administration of appropriate ICs. This vaccination technique can be used both prophylactically and therapeutically, and it mimics the immune system’s natural abilities to respond to corrective information specifically, rapidly, safely and with minimal side effects and makes this approach a novel solution for many disorders that are difficult or impossible to cure or manage.


Tolerance Modified vaccination technique Immune complex Autoantibody 











Brush border


Heymann nephritis


Immune complex


Multiple myeloma


Modified vaccination technique


Rat kidney fraction 3


Rat anti-rat kidney fraction 3



This work was supported by a Grant from an anonymous donor. All authors have contributed to, critically reviewed and approved this article. None of the authors has any conflict of interest to declare. We acknowledge the assistance of our research associate, Zoltan Kovacs, in computer and laboratory-related work.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Arpad Zsigmond Barabas
    • 1
  • Chad Douglas Cole
    • 2
  • Richard Milton Graeff
    • 3
  • Rene Lafreniere
    • 1
  • Donald Mackay Weir
    • 4
  1. 1.Department of Surgery, 2808 Health Sciences CentreUniversity of CalgaryCalgaryCanada
  2. 2.Department of NeurosurgeryUniversity of UtahSalt Lake CityUSA
  3. 3.Department of PharmacologyUniversity of MinnesotaMinneapolisUSA
  4. 4.University of Edinburgh Medical SchoolEdinburghScotland, UK

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